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Published on: September 11, 2017
Temporal Profile of MicroRNA Expression in Contused Cortex after Traumatic Brain Injury in Mice
Lilja Meissner1,2, Micaela Gallozzi1, Matilde Balbi1,2
11 Department of Neurodegeneration, Royal College of Surgeons in Ireland , Dublin, Ireland .
Abstract:
MicroRNAs (miRNAs) were recently identified as important regulators of gene expression under a wide range of physiological and pathophysiological conditions. Thus, they may represent a novel class of molecular targets for the management of traumatic brain injury (TBI). In this study, we investigated the temporal profile of miRNA expression during the development of secondary brain damage after experimental TBI. For this purpose, we used a controlled cortical impact model in C57Bl/6 mice (n = 6) to induce a cortical contusion and analyzed miRNA expression in the traumatized cortex by microarray analysis during the development of secondary contusion expansion-i.e., at 1, 6, and 12 h after TBI. Of a total 780 mature miRNA sequences analyzed, 410 were detected in all experimental groups. Of these, 158 miRNAs were significantly upregulated or downregulated in TBI compared with sham-operated animals, and 52 miRNAs increased more than twofold. We validated the upregulation of five of the most differentially expressed miRNAs (miR-21*, miR-144, miR-184, miR-451, miR-2137) and the downregulation of four of the most differentially expressed miRNAs (miR-107, miR-137, miR-190, miR-541) by quantitative polymerase chain reaction (qPCR). miR-2137, the most differentially expressed miRNA after TBI, was further investigated by in situ hybridization and was found to be upregulated in neurons within the traumatic penumbra. This study gives a comprehensive picture of miRNA expression levels during secondary contusion expansion after TBI and may pave the way for the identification of novel targets for the management of brain trauma.
Insights
MicroRNAs (miRNAs) are key gene regulators. This study reveals dynamic miRNA expression changes after traumatic brain injury (TBI), identifying potential new therapeutic targets for brain trauma management.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are critical gene expression regulators in various physiological and pathological states.
- miRNAs represent promising molecular targets for managing traumatic brain injury (TBI).
Purpose of the Study:
- To investigate the temporal expression patterns of miRNAs during secondary brain damage development following experimental TBI.
- To identify specific miRNAs that are dysregulated after TBI and could serve as therapeutic targets.
Main Methods:
- A controlled cortical impact model was used in C57Bl/6 mice to induce TBI.
- Microarray analysis was performed on traumatized cortical tissue at 1, 6, and 12 hours post-TBI to assess miRNA expression.
- Quantitative PCR (qPCR) and in situ hybridization were used for validation of key miRNA changes.
Main Results:
- Out of 780 analyzed miRNAs, 158 showed significant differential expression in TBI compared to sham controls.
- 52 miRNAs exhibited more than a twofold change, with specific miRNAs like miR-2137 being highly upregulated.
- miR-2137 was found to be upregulated in neurons within the traumatic penumbra.
Conclusions:
- This study provides a comprehensive profile of miRNA expression during the expansion of secondary contusion after TBI.
- The identified differentially expressed miRNAs, particularly miR-2137, may offer novel therapeutic targets for TBI management.
